Glutathione-depleted and cancer-targeted nanocapsules encapsulating bimetallic oxide nanoparticles for enhanced chemo-sonodynamic therapy

다국어 초록 (Multilingual Abstract)

Sonodynamic therapy (SDT) has emerged as a promising noninvasive therapeutic modality due to itsdeep tissue penetration depth. Herein, biodegradable poly(lactic-co-glycolic acid) (PLGA) nanocapsulesencapsulating oxygen-deficient MnWOx nanoparticles (NPs) and doxorubicin (DOX) were fabricatedfor chemo-sonodynamic combination therapy against cancer. To achieve cancer-targeted chemo-SDT,PLGA was conjugated to a cancer-targeting biotin through poly(ethylene glycol) (PEG).
Biotin-PEG-PLGA (BP-PLGA) nanocapsules encapsulating DOX and hydrophobic MnWOx NPs(BP-PLGA-DOX@MnWOx) exhibited high physiological stability and pH-responsive drug release. Theoxygen-deficient MnWOx NPs enabled US-triggered generation of singlet oxygen and hydroxyl radicalsowing to their oxygen-deficient structures that prevent electron–hole recombination. Glutathione(GSH) depletion by MnWOx-loaded PLGA nanocapsules was observed in MCF-7 human breast cancercells, which leads to augmented intracellular ROS levels and sonodynamic effects. Notably,BP-PLGA-DOX@MnWOx greatly improved cellular uptake by breast cancer cells, resulting in efficientintracellular delivery of DOX and MnWOx NPs. As a result, BP-PLGA-DOX@MnWOx exhibited efficientand cancer-targeted cytotoxicity in MCF-7 cells upon US irradiation. This study demonstrates that BPPLGA-DOX@MnWOx nanocapsules are promising cancer-targeting nanosonosensitizers for efficientchemo-sonodynamic cancer therapy.

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